Quantitative characterization of postnatal growth trends in proximal pulmonary arteries in rats by phase-contrast magnetic resonance imaging

Abstract

Malformations of the pulmonary arteries can increase right heart workload and result in morbidity, heart failure, and death. With the increased use of murine models to study these malformations, there is a pressing need for an accurate and noninvasive experimental technique that is capable of characterizing pulmonary arterial hemodynamics in these animals. We describe the growth trends of pulmonary arteries in 13 male Sprague-Dawley rats at 20, 36, 52, 100, and 160 days of age with the introduction of phase-contrast MRI as such a technique. PCMRI results correlated closely with cardiac output measurements by ultrasound echocardiography and with fluorescent microspheres in right-left lung flow split (flow partition). Mean flow, average cross-sectional area, distensibility, and shear rates for the right and left pulmonary arteries (RPA and LPA) were calculated. The RPA was larger and received more flow at all times than the LPA (P < 0.0001). Right-left flow split did not change significantly with age, and arterial distensibility was not significantly different between RPA and LPA, except at 160 days (P < 0.01). Shear rates were much higher for the LPA than the RPA (P < 0.0001) throughout development. The RPA and LPA showed different structure-function relationships but obeyed similar allometric scaling laws, with scaling exponents comparable to those of the main pulmonary artery. This study is the first to quantitatively describe changes in RPA and LPA flows and sizes with development and to apply phase-contrast MRI techniques to pulmonary arteries in rats.

Chronic effects of pulmonary artery stenosis on hemodynamic and structural development of the lungs

“…Our PCMRI techniques (29) have enabled in vivo measurements of vessel size and pulmonary flow that indicate that pulmonary arterial banding results in lowered flow and smaller lumen sizes throughout development. We show, for the first time, that the wall shear autoregulatory phenomenon (18,32,43) that has been proposed as the biomechanical factor dictating vessel caliber in systemic arteries also holds in the case of the pulmonary arteries.…”

“…Measurements of pulmonary arterial blood flow in vivo were conducted according to techniques described previously in detail (29).…”

“…To elucidate the chronic changes that occur in response to a partial pulmonary arterial obstruction in neonates, as most closely related to clinical CHD cases such as repaired Tetralogy of Fallot, we banded the LPA of neonatal rats and studied the functional and structural changes that ensued as the animals grew to adulthood. In this study, we aimed to assess the impact of pulmonary artery stenosis on lung development using new imaging techniques recently developed and validated by our group (29). We describe how increased and decreased pulmonary flows result in major structural changes and provide insight for clinicians in care of children with CHDs.…”

Macitentan reverses early obstructive pulmonary vasculopathy in rats: early intervention in overcoming the survivin-mediated resistance to apoptosis

“…Transthoracic two-dimensional and pulsed-wave Doppler modes were used to obtain the triplet of main pulmonary artery (PA) diameter measurements and the five velocity-time integral measurements close to the center of the vessel. Echocardiographically derived cardiac output was calculated with the formula [(main PA area) ϫ (main PA velocity-time integral) ϫ heart rate] as published previously (29).…”

“Real-time visualization of lung function: from micro to macro”

“…The number of repeat measurements is limited only by exposure to radiation, which applies largely to CAT studies. Indeed, studies have reported the monitoring of postnatal pulmonary artery growth at regular intervals for up to 160 days by phase-contrast MRI (22), highlighting the usefulness of noninvasive, nonterminal radiological approaches to study lung structure and function. In terms of airway function, synchrotron radiation computed tomography (CT) imaging has recently been very elegantly used to differentiate central vs. peripheral airway and lung parenchymal components of the response to airway provocation by cigarette smoke (19), and single proton emission computed tomography (SPECT) to quantify clearance of intratracheally delivered 99m Tc-diethylene triamine pentaacetic acid has been used to assess airway barrier function (26).…”